Parathyroid hormone-related protein (PTHrP) inhibits proliferation of Chinese hamster ovary cells stably transfected with a PTH/PTHrP receptor cDNA.
The effect of parathyroid hormone-related protein (PTHrP) on proliferation was examined in Chinese hamster ovary (CHO) cells transfected with a PTH/PTHrP receptor encoding cDNA. Treatment with chicken PTHrP(1-36) (chPTHrP) lowered the cell number to 49 +/- 2% of untreated controls after 6 days with a half-maximal effect at 1 nM. The effect was mimicked by human (h) PTH(1-34), Br-cAMP and forskolin, but not by the receptor antagonist hPTH(3-34). Reduction of cell number was accompanied by increased PTH/PTHrP receptor expression and persistently activated adenylyl cyclase, together with altered cell morphology from epithelial to spindle-like forms, clustered growth and increased phosphate uptake. chPTHrP increased [Ca2+]i, but failed to activate membrane bound protein kinase C (PKC). Pretreatment with chPTHrP did not affect phorbol ester stimulated PKC activity, and chPTHrP or serum evoked increases in [Ca2+]i. In conclusion, PTHrP induced inhibition of proliferation and altered cell morphology is mediated by increased adenylyl cyclase rather than by PKC-dependent mechanisms in CHO cells.
Muff
R
R
Department of Orthopedic Surgery, University of Zurich, Switzerland. ramuz@balgrist.unizh.ch
Kaufmann
M
M
Born
W
W
Fischer
J A
JA
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D016466:CHO Cells; D002118:Calcium / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects*; D005576:Colforsin / Q000494:pharmacology; D006224:Cricetinae; D000242:Cyclic AMP / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D044162:Parathyroid Hormone-Related Protein; D010710:Phosphates / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D011506:Proteins / Q000494:pharmacology*; D044168:Receptor, Parathyroid Hormone, Type 1; D018016:Receptors, Parathyroid Hormone / Q000235:genetics / Q000502:physiology*; D019379:Teriparatide / Q000494:pharmacology; D014162:Transfection
C470121:PTHLH protein, human; D044162:Parathyroid Hormone-Related Protein; D010710:Phosphates; D011506:Proteins; D044168:Receptor, Parathyroid Hormone, Type 1; D018016:Receptors, Parathyroid Hormone; D019379:Teriparatide; D005576:Colforsin; D015124:8-Bromo Cyclic Adenosine Monophosphate; D000242:Cyclic AMP; D011493:Protein Kinase C; D002118:Calcium